scholarly journals Genetically determined body mass index mediates the effect of smoking on type 2 diabetes risk, but not coronary artery disease risk

2020 ◽  
Author(s):  
Christopher S Thom ◽  
Zhuoran Ding ◽  
Michael G Levin ◽  
Scott M Damrauer ◽  
Benjamin F Voight
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Smoking Behavior ◽  
Diabetes Risk ◽  
Artery Disease ◽  
Genetically Determined ◽  
Randomization Analysis

AbstractClinical observations have linked tobacco smoking with increased type 2 diabetes risk (1–5), a major public health concern (6). Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes (7). However, this initial association could be mediated by additional causal risk factors correlated with smoking behavior, which have not been investigated to date. We hypothesized that body mass index (BMI) could explain the association between smoking and diabetes risk. First, we confirmed previous reports that genetically determined smoking behavior increased risk for both type 2 diabetes (OR=1.21, 95% CI: 1.15-1.27, P=1×10−12) and coronary artery disease (CAD; OR=1.21, 95% CI: 1.16-1.26, P=2×10−20). Additionally, a 2-fold increased smoking risk is positively associated with body mass index (BMI; ∼0.8 kg/m2, 95% CI: 0.54-0.98 kg/m2, P=1.8×10−11). In multivariable Mendelian randomization analysis, including BMI accounted for nearly all of the risk of smoking on type 2 diabetes (OR 1.06, 95% CI: 1.01-1.11, P=0.03). In contrast, the independent association between smoking and CAD persisted (OR 1.12, CI: 1.08-1.17, P=3×10−8) despite controlling for BMI. Causal mediation analyses agreed with these estimates. Our findings support a model whereby smoking initiation increases obesity, which in turn increases type 2 diabetes risk, with minimal if any direct effects from smoking on diabetes risk. Patients should be advised to stop smoking to limit both type 2 diabetes and CAD risk, and therapeutic efforts should consider pathophysiology relating smoking and obesity.

scholarly journals Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease

2020 ◽  
Vol 29 (19) ◽  
pp. 3327-3337
Author(s):  
Christopher S Thom ◽  
Zhuoran Ding ◽  
Michael G Levin ◽  
Scott M Damrauer ◽  
Kyung Min Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Mendelian Randomization ◽  
Smoking Behavior ◽  
Diabetes Risk ◽  
Genetic Determinants ◽  
Increased Risk ◽  
Artery Disease ◽  
Cad Risk

Abstract Clinical observations have linked tobacco smoking with increased type 2 diabetes risk. Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes. However, this association could be mediated by additional risk factors correlated with smoking behavior, which have not been investigated. We hypothesized that body mass index (BMI) could help to explain the association between smoking and diabetes risk. First, we confirmed that genetic determinants of smoking initiation increased risk for type 2 diabetes (OR 1.21, 95% CI: 1.15–1.27, P = 1 × 10−12) and coronary artery disease (CAD; OR 1.21, 95% CI: 1.16–1.26, P = 2 × 10−20). Additionally, 2-fold increased smoking risk was positively associated with increased BMI (~0.8 kg/m2, 95% CI: 0.54–0.98 kg/m2, P = 1.8 × 10−11). Multivariable Mendelian randomization analyses showed that BMI accounted for nearly all the risk smoking exerted on type 2 diabetes (OR 1.06, 95% CI: 1.01–1.11, P = 0.03). In contrast, the independent effect of smoking on increased CAD risk persisted (OR 1.12, 95% CI: 1.08–1.17, P = 3 × 10−8). Causal mediation analyses agreed with these estimates. Furthermore, analysis using individual-level data from the Million Veteran Program independently replicated the association of smoking behavior with CAD (OR 1.24, 95% CI: 1.12–1.37, P = 2 × 10−5), but not type 2 diabetes (OR 0.98, 95% CI: 0.89–1.08, P = 0.69), after controlling for BMI. Our findings support a model whereby genetic determinants of smoking increase type 2 diabetes risk indirectly through their relationship with obesity. Smokers should be advised to stop smoking to limit type 2 diabetes and CAD risk. Therapeutic efforts should consider pathophysiology relating smoking and obesity.

scholarly journals Homogeneity in the association of body mass index with type 2 diabetes across the UK Biobank: A Mendelian randomization study

PLoS Medicine ◽  
2019 ◽  
Vol 16 (12) ◽  
pp. e1002982 ◽  
Author(s):  
Michael Wainberg ◽  
Anubha Mahajan ◽  
Anshul Kundaje ◽  
Mark I. McCarthy ◽  
Erik Ingelsson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
The Uk

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽  
2022 ◽  
Author(s):  
Maddalena Ardissino ◽  
Eric A.W. Slob ◽  
Ophelia Millar ◽  
Rohin K. Reddy ◽  
Laura Lazzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

scholarly journals Distribution of Helicobacter pylori infection and abnormal body- mass index (BMI) in a developing country

2018 ◽  
Vol 12 (05) ◽  
pp. 342-346 ◽  
Author(s):  
Basit Siddiqui ◽  
Javed Yakoob ◽  
Zaigham Abbas ◽  
Rabeea Azmat ◽  
Syeda Sadia Fatima ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Helicobacter Pylori ◽  
Body Mass ◽  
Cross Sectional Study ◽  
Comorbid Conditions ◽  
Cross Sectional ◽  
Artery Disease ◽  
H Pylori

Introduction: Helicobacter pylori is prevalent in developing nations. We determined the prevalence of H. pylori infection in relation to body-mass index (BMI) of dyspeptic patients and related comorbid conditions. Methodology: In a cross-sectional study, dyspeptic patients were enrolled and tested for H. pylori infection. “Underweight” was defined as BMI lower than 18.4; “Healthy” 18.5 to 23; “Overweight” 23.1-27.9; and “Obese” greater than 28. Results: Six hundred and ninety-eight patients were included, with a mean age of 44 ± 16 years. Males were 373/698, 53%. H. pylori was positive in 399/698, 57%. Underweight were 36 (5%); BMI-healthy 168 (24%); overweight 236 (34%) and obese 258 (37%). H. pylori infection was present in 65/273 BMI-healthy patients ; 24% compared to obese 208/273; 76% (P < 0.001). In the H. pylori- positive with a “healthy” BMI, dyslipidemia was seen in 6/65; 8% compared to obese 53/208; 25% (P = 0.005); type 2 diabetes in 8/65; 12% with a “healthy” BMI compared to obese 54/208; 26% (P = 0.022) and coronary artery disease in 4/65; 6% of BMI-healthy compared to obese 38/208; 18% patients (P = 0.018). Multivariate analysis showed that age 31-50 years (OR 1.77, 95% CI 1.13-2.77), BMI > 23.1 (OR 2.91, 95% CI infection. 2.01-4.20), and type 2 diabetes (OR 2.41, 95% CI 1.43-4.06) were risk factors for H. pylori Conclusions: H. pylori infection was prevalent in the 31-50-year age group. Abnormal BMI was associated with H. pylori infection.

scholarly journals Genetic comorbidity between major depression and cardio-metabolic disease, stratified by age at onset of major depression

2019 ◽  
Author(s):  
SP Hagenaars ◽  
JRI Coleman ◽  
S Choi ◽  
H Gaspar ◽  
MJ Adams ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Body Mass Index ◽  
Coronary Artery ◽  
Major Depression ◽  
Body Mass ◽  
Genetic Correlations ◽  
Polygenic Risk ◽  
Artery Disease

AbstractIntroductionIt’s imperative to understand the specific and shared aetiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression.MethodsPolygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic aetiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in eleven data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank.ResultsAll cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression.ConclusionsThe phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic aetiology irrespective of the age depression first presents.

scholarly journals Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1971-1979
Author(s):  
Sabine van Oort ◽  
Joline W.J. Beulens ◽  
Adriana J. van Ballegooijen ◽  
Diederick E. Grobbee ◽  
Susanna C. Larsson
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Educational Level ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lifestyle Behaviors ◽  
Prevention Of Hypertension

Hypertension is a major risk factor for cardiovascular disease and mortality. To identify targets for the prevention of hypertension and its associated disease burden, we used the 2-sample Mendelian randomization method to investigate the causal associations of 18 cardiovascular risk factors and lifestyle behaviors with hypertension. From European-descent genome-wide association studies, we selected genetic variants ( P <5×10 −8 ) for type 2 diabetes, fasting glucose, lipids, body mass index, smoking, alcohol and coffee consumption, physical activity, sleep duration, insomnia, and educational level. We extracted the genetic associations with hypertension from 2 European cohorts: the FinnGen Study (15 870 cases and 74 345 controls) and UK Biobank (54 358 cases and 408 652 controls). The inverse-variance weighted method was used as main analysis method. Genetically predicted triglycerides (pooled odds ratio [OR] per 1 SD, 1.17 [1.10–1.25]), body mass index (OR per 1 SD, 1.42 [1.37–1.48]), alcohol dependence (OR, 1.10 [1.06–1.13]), and insomnia (OR, 1.17 [1.13–1.20]) were associated with a higher odds of hypertension. Higher genetically predicted high-density lipoprotein cholesterol (OR per 1 SD, 0.88 [0.83–0.94]) and educational level (OR per 1 SD, 0.56 [0.54–0.59]) were associated with a lower odds of hypertension. Suggestive evidence was obtained for type 2 diabetes, smoking initiation and alcohol consumption with a higher hypertension odds, and longer sleep duration with a lower hypertension odds. This Mendelian randomization study identified high-density lipoprotein cholesterol, triglycerides, body mass index, alcohol dependence, insomnia, and educational level as causal risk factors for hypertension. This implicates that these modifiable risk factors are important targets in the prevention of hypertension.

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